Hovilpri (pritelivir)

Refractory mucocutaneous herpes simplex virus (HSV) infection is defined in the Hovilpri prescribing information as no clinical improvement after at least 7 days of acyclovir, valacyclovir, or famciclovir, with or without laboratory-confirmed resistance. A 2025 consensus definition describes resistant infection as refractory infection with genotypic or phenotypic evidence of decreased drug susceptibility. Reported rates differ across studies. The consensus review gives resistance rates of often 0% to 14% in hematopoietic cell transplant (HCT) recipients, 0% to 3% in solid organ transplant recipients, and 3% to 7% in advanced HIV disease. For HCT recipients, a narrative review cites small studies reporting up to 46% and a systematic review reports a median incidence of 16.1%. Laboratory-confirmed acyclovir-resistant infection occurred in 18 recipients (0.4%) among 4,028 allogeneic HCTs performed at one U.S. cancer center, and 12 of 226 HIV-positive U.S. clinic participants (5.3%) had resistant isolates. The report found no population-based U.S. estimate of refractory infection. Asahi Kasei estimates, from an internal investigation, approximately 15,000 immunocompromised people in the United States at second-line treatment.

In a cohort of 125 HCT recipients with refractory infection at 7 U.S. centers, 69 participants (55.2%) healed completely at a median of 38 days and 40 (32.0%) died on therapy. Of the 69 who healed, 27 (39.1%) had a recurrence and 22 (31.9%) died within 1 year. In a 5-center U.S. cohort, 15 of 31 foscarnet-treated episodes (48%) healed and 8 of those 15 (53%) recurred. In a single-center U.S. cohort of 18 allogeneic HCT recipients, 9 (50%) were hospitalized and 9 (50%) died within 1 year. Foscarnet in the 7-center cohort was given in a hospital or hospital-associated infusion clinic for a mean of 21.8 days. The report found no quality-of-life study using a validated instrument and no cost or length-of-stay study of this condition.

A federal HIV guideline (AI) and a 2009 HCT guideline (BI) name intravenous foscarnet as the treatment of choice, and 2007 European leukemia recommendations rate it BIII. The alternatives are intravenous cidofovir, rated CIII in the HIV and HCT guidelines, and topical imiquimod, cidofovir, trifluridine, and foscarnet, rated BIII in the HIV guideline. The foscarnet label carries a boxed warning for renal impairment and seizures and requires intravenous infusion by pump, with hydration. In the 7-center cohort, toxicity was reported during 75 of 109 foscarnet courses (68.8%), renal function abnormalities during 44 (40.4%), and discontinuation for toxicity in 33 (30.3%). A 2025 review states that, apart from two small randomized trials in people with HIV in the 1990s, treatment recommendations rest on observational studies and case reports.

• Design: PRIOH-1 Part C (NCT03073967) was a phase 3, randomized, open-label comparison of oral pritelivir (400 mg on day 1, then 100 mg once daily) with investigator's choice (intravenous foscarnet in 70% of that arm; otherwise cidofovir or topical imiquimod) for up to 28 days, or 42 days if lesions were improving, in immunocompromised adults with mucocutaneous HSV infection refractory to acyclovir, valacyclovir, or famciclovir, with or without documented resistance. Of 102 participants randomized, 101 were treated (51 pritelivir, 50 investigator's choice). The registry lists 70 locations and an enrollment of 158; other sources print 153 or 157 participants, 60 or 66 sites, and 12, 14, or 15 countries.
• Primary efficacy: in the prescribing information, all lesions healed within 28 days in 32 of 51 participants (63%) on pritelivir and 17 of 50 (34%) on investigator's choice (adjusted difference 28.4; 95% CI 9.6 to 47.3; p = 0.0047). The congress presentations print 62.7% and 34.0% with the same adjusted difference, confidence interval, and P value.
• Secondary and subgroup results: healing up to day 42 was 82% and 42% in the label (adjusted difference 40%; 95% CI 22.7 to 57.7); the congress presentation prints 82.4%, 42.0%, and 40.2% (p<0.0001). Median time to undetectable HSV DNA in lesions was 9 and 21 days (hazard ratio 1.76; 95% CI 0.98 to 3.16; p = 0.0581). Day 28 healing was 14 of 23 (61%) and 3 of 15 (20%) among all participants living with HIV, a post hoc analysis (p = 0.027); 8 of 16 (50.0%) and 11 of 28 (39.3%) among transplant recipients; and 11 of 22 (50.0%) and 10 of 34 (29.4%) with laboratory-confirmed acyclovir resistance. The 95% CI of the difference includes zero in the last two subgroups.
• Parts D to F and phase 2: single-arm Parts D and F enrolled 35 participants refractory to acyclovir and foscarnet or foscarnet intolerant; lesions healed in 40% up to 28 days and 66% up to 42 days. Part E treated 21 participants with acyclovir-sensitive infection; no result was found. Phase 2 Part A randomized 22 participants to pritelivir (15) or intravenous foscarnet (7): the hazard ratio for the primary endpoint, time to healing by independent photographic review, was 2.70 (P = .34), and investigators recorded healing in 14 of 15 (93.3%) and 4 of 7 (57.1%). In open-label Part B, 5 of 8 participants (62.5%) healed.
• Safety: in the label, headache was the adverse reaction in more than 5% of pritelivir recipients (6%, and 4% on investigator's choice); adverse reactions occurred in 22% and 54%, and discontinuations due to adverse drug reactions in 2% and 20%. The congress presentation reports serious adverse events in 10 (19.6%) and 15 (30.0%) and renal or urinary disorders in 3 (5.9%) and 13 (26.0%). The label lists no contraindications and one warning: certain acid-reducing agents may reduce pritelivir exposure. It reports pUL5 substitutions with reduced susceptibility in 4 phase 3 participants and 1 phase 2 participant.
• Other populations and clinical pharmacology: in adults with genital HSV-2, the placebo-controlled trial AIC316-01-II-01 (156 randomized) found shedding rates of 16.6% with placebo and 2.1% with pritelivir 75 mg daily (relative risk 0.13). The crossover trial AIC316-01-II-02 detected HSV in 2.4% of swabs on pritelivir 100 mg and 5.3% on valacyclovir 500 mg (relative risk 0.42); it randomized 91 of 98 planned participants and was terminated after the FDA imposed a clinical hold in May 2013, based on hematologic and dermatologic findings in a chronic toxicity study in monkeys. In the thorough QT trial, the placebo-corrected QTcF change predicted at the mean maximum concentration was 0.8 ms (90% CI -1.3 to 2.9). Esomeprazole 40 mg decreased pritelivir AUC by approximately 59%, and pritelivir increased rosuvastatin AUC 1.4-fold. The label recommends no dose adjustment in mild to severe renal impairment or in mild or moderate hepatic impairment.
• Evidence gaps: as of October 2026, no full peer-reviewed publication of Part C was found, and the registry has no posted results. Part C was open-label with investigator-assessed healing, and 23 of 50 comparator participants (46%) did not complete treatment. No evidence was found for time to lesion healing, recurrence, pain, or quality-of-life results in Part C, or for any Part E result. Participants with ocular, central nervous system, or disseminated HSV disease were not enrolled.

No published budget impact model, cost-effectiveness analysis, or health technology assessment of pritelivir has been identified. The FDA approved pritelivir on 9 October 2026, the manufacturer expects availability in the United States before the end of 2026, and no published wholesale acquisition cost (WAC) has been identified. The one figure identified is a market research assumption in a 2025 AiCuris corporate presentation: a monthly per-patient WAC in the United States of approximately $30,000, assuming a 28-day treatment course. The labeled dose is 400 mg on day 1, then 100 mg once daily until the lesions have healed. In the trial the label describes, treatment lasted up to 28 days, or up to 42 days when lesions were improving; the mean duration among 51 participants was 27.1 days, and 33% extended treatment up to 42 days. The label lists cartons of 16 and 32 tablets.

For the eligible population, Asahi Kasei estimates approximately 180,000 people in the United States at first-line treatment and 15,000 at second-line treatment, based on an internal investigation. A 2024 AiCuris presentation gives a different company estimate, 27,200 severely immunocompromised people with acyclovir resistance in the United States. Published figures include a 0.4% incidence of laboratory-confirmed acyclovir-resistant infection among 4,028 allogeneic transplants at one center and, in a 2025 review, resistance rates of often 0% to 14% in hematopoietic cell transplant recipients. For the comparator, a cohort from 7 United States transplant centers reports 109 foscarnet courses of a mean 21.8 days in a hospital or hospital-associated infusion clinic, a 5-center cohort reports a median of 16 days, and a single-center cohort reports hospitalization in 9 of 18 recipients (50%). The fourth-quarter 2026 Medicare Clinical Laboratory Fee Schedule lists $26.07 and $20.20 for the codes of the Labcorp phenotypic resistance test and $35.09 and $130.35 for the codes of the University of Washington genotypic tests. This report holds no cost study of refractory infection, no foscarnet course cost, and no payment limit.

The FDA approved pritelivir (Hovilpri) on 9 October 2026 for immunocompromised adults, for the treatment of mucocutaneous lesions caused by herpes simplex virus (HSV) infection that is refractory, with or without documented resistance, to acyclovir, valacyclovir, or famciclovir. The oral regimen is 400 mg on day 1, then 100 mg once daily until the lesions have healed. Hovilpri received priority review, and the manufacturer reports Fast Track and Breakthrough Therapy designations. The pivotal evidence is PRIOH-1 Part C, a phase 3, randomized, open-label trial in which 101 participants were treated with pritelivir (51) or investigator's choice (50): intravenous foscarnet in 70% and otherwise cidofovir or topical imiquimod. In the prescribing information, all lesions healed within 28 days in 32 of 51 participants (63%) and 17 of 50 (34%) (adjusted difference 28.4; 95% CI 9.6 to 47.3; p = 0.0047), and healing up to day 42 was 82% and 42% (adjusted difference 40%; 95% CI 22.7 to 57.7). Adverse reactions were reported in 22% and 54% of participants, and discontinuations due to adverse drug reactions in 2% and 20%. The label lists no contraindications and one warning: certain acid-reducing agents may reduce pritelivir exposure.

Part C was open-label with investigator-assessed healing. As of October 2026, no full peer-reviewed publication of it was found, and the registry has no posted results. No evidence was found for time to lesion healing, recurrence, pain, or quality of life in Part C. The 95% CI of the day 28 difference includes zero among transplant recipients (50.0% and 39.3% healed) and participants with laboratory-confirmed acyclovir resistance (50.0% and 29.4%). The single-arm Parts D and F enrolled 35 participants refractory to acyclovir and foscarnet or foscarnet intolerant; lesions healed in 40% up to 28 days and 66% up to 42 days. The label reports pUL5 substitutions with reduced susceptibility in 4 phase 3 participants. Participants with ocular, central nervous system, or disseminated HSV disease were not enrolled. No published wholesale acquisition cost, budget impact model, cost-effectiveness analysis, or health technology assessment has been identified. Asahi Kasei estimates, from an internal investigation, approximately 15,000 people in the United States at second-line treatment, and a 2024 AiCuris presentation gives 27,200 severely immunocompromised people with acyclovir resistance. The manufacturer expects availability in the United States before the end of 2026.